Document 0173
 DOCN  M9620173
 TI    Mutation of Jak3 in a patient with SCID: essential role of Jak3 in
       lymphoid development.
 DT    9602
 AU    Russell SM; Tayebi N; Nakajima H; Riedy MC; Roberts JL; Aman MJ; Migone
       TS; Noguchi M; Markert ML; Buckley RH; et al; Laboratory of Molecular
       Immunology, National Heart, Lung, and; Blood Institute (NHLBI), National
       Institutes of Health (NIH),; Bethesda, MD 20892, USA.
 SO    Science. 1995 Nov 3;270(5237):797-800. Unique Identifier : AIDSLINE
       MED/96055115
 AB    Males with X-linked severe combined immunodeficiency (XSCID) have
       defects in the common cytokine receptor gamma chain (gamma c) gene that
       encodes a shared, essential component of the receptors of interleukin-2
       (IL-2), IL-4, IL-7, IL-9, and IL-15. The Janus family tyrosine kinase
       Jak3 is the only signaling molecule known to be associated with gamma c,
       so it was hypothesized that defects in Jak3 might cause an XSCID-like
       phenotype. A girl with immunological features indistinguishable from
       those of XSCID was therefore selected for analysis. An Epstein-Barr
       virus (EBV)-transformed cell line derived from her lymphocytes had
       normal gamma c expression but lacked Jak3 protein and had greatly
       diminished Jak3 messenger RNA. Sequencing revealed a different mutation
       on each allele: a single nucleotide insertion resulting in a frame shift
       and premature termination in the Jak3 JH4 domain and a nonsense mutation
       in the Jak3 JH2 domain. The lack of Jak3 expression correlated with
       impaired B cell signaling, as demonstrated by the inability of IL-4 to
       activate Stat6 in the EBV-transformed cell line from the patient. These
       observations indicate that the functions of gamma c are dependent on
       Jak3 and that Jak3 is essential for lymphoid development and signaling.
 DE    Amino Acid Sequence  Animal  B-Lymphocytes/*IMMUNOLOGY  Base Sequence
       Case Report  Cell Line, Transformed  Female  Frameshift Mutation  Human
       Infant  Interleukin-4/PHARMACOLOGY  Linkage (Genetics)  Molecular
       Sequence Data  Phenotype  Point Mutation  Protein-Tyrosine
       Kinase/DEFICIENCY/GENETICS/*PHYSIOLOGY  Receptors,
       Interleukin/PHYSIOLOGY  RNA, Messenger/GENETICS/METABOLISM  Severe
       Combined Immunodeficiency/*ENZYMOLOGY/GENETICS/IMMUNOLOGY  Signal
       Transduction  Support, U.S. Gov't, P.H.S.  T-Lymphocytes/*IMMUNOLOGY
       Trans-Activators/METABOLISM  X Chromosome  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).